Publication details

How does hydroxyl introduction influence the double helical structure: the stabilization of an altritol nucleic acid: ribonucleic acid duplex

Authors

OVAERE Margriet ŠPONER Jiří ŠPONEROVÁ Judit HERDEWIJN Piet VAN MEERVELT Luc

Year of publication 2012
Type Article in Periodical
Magazine / Source Nucleic Acids Research
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://nar.oxfordjournals.org/content/early/2012/05/24/nar.gks470.short
Doi http://dx.doi.org/10.1093/nar/gks470
Field Biophysics
Keywords BASIS-SET CONVERGENCE; DNA-BASE PAIRS; INTERACTION ENERGIES; CRYSTAL-STRUCTURE; MODIFIED SIRNAS; MODEL; RI-MP2; REFINEMENT; EFFICIENCY; COMPLEXES
Attached files
Description Altritol nucleic acids (ANAs) are a promising new tool in the development of artificial small interfering ribonucleic acids (siRNAs) for therapeutical applications. To mimic the siRNA: messenger RNA (mRNA) interactions, the crystal structure of the ANA: RNA construct a(CCGUAAUGCC-P):r(GGCAUUACGG) was determined to 1.96 angstrom resolution which revealed the hybrid to form an A-type helix. As this A-form is a major requirement in the RNAi process, this crystal structure confirms the potential of altritol-modified siRNAs. Moreover, in the ANA strands, a new type of intrastrand interactions was found between the O2' hydroxyl group of one residue and the sugar ring O4' atom of the next residue. These interactions were further investigated by quantum chemical methods. Besides hydration effects, these intrastrand hydrogen bonds may also contribute to the stability of ANA: RNA duplexes.
Related projects: